by Gabriel Carabulea, M.D.
Almost 80% of men currently diagnosed with prostate cancer undergo a biopsy due to a suspicious serum prostate specific antigen (PSA). However, digital rectal examination (DRE) retains an important role for early detection as 20% of cases have a prostate nodule that prompts the biopsy.
Asymmetric areas of induration or frank nodules are suggestive of prostate cancer. A prostate biopsy is indicated in men with a digital rectal examination that is suspicious for cancer, regardless of the serum PSA. In contrast, symmetric enlargement and firmness of the prostate are more frequent in men with benign prostatic hyperplasia (BPH).
PSA is a protein made solely by prostate cells so the antigen is highly specific for the prostate. However, it is not prostate cancer specific and other prostate conditions such as benign prostatic hyperplasia (BPH) or prostatitis can affect PSA levels. The lack of specificity for prostate cancer has led to considerable controversy about the role of routine PSA testing.
Although more cancers are found through PSA screening, many men undergo a biopsy which may prove to be negative or are subjected to treatment and its side effects for a cancer that may not be life threatening. This has led the 2012 U.S Preventive Services Task Force recommendation to omit PSA screening from routine primary care. Targeting screening to the most optimal population (those with at least 10 years of life expectancy) and personalized screening strategies that are tailored to a man’s individual risk and preferences may be a more appropriate guide to prostate cancer screening.
Transrectal ultrasonography (TRUS) is often used to evaluate abnormalities detected by digital rectal examination and to guide sites for prostate biopsy. However, prostate biopsy is recommended regardless of the results, since TRUS misses a substantial number of tumors.
Most men with early stage prostate cancer have no symptoms attributable to the cancer.
Urinary frequency, urgency, nocturia and hesitancy are seen commonly but are usually related to a concomitant benign prostate enlargement.
Men with abnormal prostate exams (nodules, induration, or asymmetry) should be referred to an urologist for a prostate biopsy, with a histologic diagnosis based upon tissue obtained from the biopsy. A prostate biopsy may also be indicated based upon abnormal PSA values. If a biopsy is to be performed based upon the finding of an elevated serum PSA, confirmation of the elevated serum PSA is advisable prior to proceeding to prostate biopsy.
If cancer is found in the prostate biopsy, the amount of cancer and aggressiveness of the tumor will be determined. The Gleason grade depends on how the tumor looks under the microscope. The higher the Gleason grade, the more likely the tumor is to behave aggressively (grow faster).
Over the last 20 years, more men are being diagnosed with prostate cancer at an early stage, when the cancer is highly curable.
Prostate cancer stage
Once prostate cancer is diagnosed, the next step is to determine its stage. Staging is a system used to describe the size, aggressiveness and spread of a cancer. A cancer’s stage helps to guide treatment and can help predict the chance of curing the cancer. In addition, the PSA (prostate-specific antigen) level and the Gleason grade are used to gauge how aggressive the tumor is, and what treatment options are available.
Localized prostate cancer- stage I and II - is cancer that has not spread to the lymph nodes or distant organs. There are three standard ways to treat localized prostate cancer: surgery, radiation therapy, and active surveillance also called “watch and wait.” The best treatment depends upon age and health, preferences, and the stage of the cancer.
Radical prostatectomy (also called prostatectomy) is a surgery done to remove the prostate gland and then reconnect the urethra. The most common complications of prostatectomy are urinary incontinence, and erectile dysfunction (ED).
Radiation Therapy (RT)
Two forms of RT are used to treat prostate cancer: external beam RT and brachytherapy. These are sometimes used together. External beam RT (EBRT) uses a machine that moves around you, directing X-rays at the pelvis. EBRT is typically done daily five days per week, for five to eight weeks. In brachytherapy, a doctor places a radioactive source directly into the prostate gland.
Some men choose to delay prostate cancer treatment, opting for a strategy called active surveillance. During active surveillance one or more additional prostate biopsies may be required and monitored carefully for signs of cancer growth, with an exam and blood tests every three to six months. Using this approach, may avoid or postpone treatment for long periods of time. Active surveillance may be a reasonable option if the cancer is very small and unlikely to grow quickly.
Androgen Deprivation Therapy (ADT)
Male hormones (androgens, the most common of which is testosterone) fuel the growth of prostate cancer. Treatments that decrease the body's levels of androgens (called androgen deprivation therapy, or ADT) decrease the size and slow the growth of prostate cancer.
ADT is not needed for men with small tumors that are unlikely to grow quickly. ADT might be recommended, in addition to EBRT, for men with intermediate and high-risk prostate cancer. Examples of the medicines used in ADT include: GnRH agonists (Lupron, Zoladex), and antiandrogens.
Treatment of rising PSA
After treatment for localized prostate cancer, experts advise follow-up testing to monitor for signs that the cancer has returned. This follow-up testing usually includes a blood test called PSA (prostate-specific antigen). The PSA test is very sensitive, meaning that the PSA may begin to rise well before the return of the cancer can be seen or felt. Many men with a rising PSA will not have any sign that the cancer has come back for many years (even 15 or more). Thus, not all men with a rising PSA need immediate treatment.
Which treatment is right for me?
Advanced prostate cancer is usually managed with a combination of treatments, which may include hormone therapy, chemotherapy, immunotherapy, or radiation. For men with early-stage (localized) prostate cancer, the decision between radiation therapy (RT) and surgery is largely a matter of preference. Always talk to your doctor to discuss and understand your options.
Secondary Hormone Therapy
Most men with advanced prostate cancer initially respond well to ADT, but then the prostate cancer comes back. At this point, the cancer is termed “castrate resistant,” meaning that ADT alone is no longer effective. Once this occurs, secondary hormone therapy is usually considered.
A newer approach to treating advanced prostate cancer involves harnessing or strengthening the body’s own immune response to attack the cancer. One form of immunotherapy involves the use of cancer vaccines. Another form involving the use of so-called monoclonal antibodies is under investigation.
Chemotherapy is commonly given to men with advanced prostate cancer who have stopped responding to all forms of hormone therapy. Recent clinical trials have shown that when chemotherapy is given earlier it may improve how long a man will live.
New genetic tests are being developed to support treatment decisions in prostate cancer. A genomic classifier is now available that can indicate a low or high risk for metastasis in men with prostate cancer who have rising prostate-specific antigen (PSA) after a prostatectomy. This test can prevent overtreatment and undertreatment of men with prostate cancer. Men with a low genomic classifier score can safely delay radiation therapy, and may not need further salvage therapy.
Immunotherapy and targeted therapies are opening new possibilities in the treatment of prostate cancer. The researchers have found that nearly all the tumors have at least one genetic aberration known to drive cancers. The most common are abnormalities in genes responsible for the androgen receptor.
Also, prostate cancer cells express a number of tumor-associated antigens that can serve as targets for immunotherapy. Sipuleucel-T (Provenge) is an autologous dendritic cell therapeutic vaccine designed to enhance the immune T cell response. In randomized trials, sipuleucel-T prolonged survival compared to placebo dendritic cells and had a favorable safety profile.
The next generation chemotherapy for prostate cancer has unique properties that could make it more effective earlier in treatment if confirmed in clinical trials. A newer member of the taxane family called cabazitaxel, an FDA approved drug, has properties that could make it more effective for some patients - a hypothesis currently being tested in clinical trials.